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Biomedical subjects

H Sano

Publications and source records attributed to H Sano.

At least 217 records · Page 12Linked to original sources

Receptors for proteins modified by advanced glycation endproducts (AGE)--their functional role in atherosclerosis.

Long-term incubation of proteins with glucose leads, through the formation of early stage products such as Schiff base and Amadori rearrangement products, to the formation of advanced glycation end products (AGE). Recent studies of AGE-structures as well as the receptor for AGE-proteins (AGE-receptors) have emphasized the involvement of protein modification by AGE in aging and age-enhanced disease processes. Immunohistochemical analyses of human atherosclerotic lesions using a monoclonal anti-AGE antibody have demonstrated diffuse extracellular AGE-deposition as well as dense intracellular AGE-deposition in macrophage- and vascular smooth muscle cell (SMC)-derived foam cells. In vitro experiments using both CHO cells overexpressing macrophage scavenger receptor-A (MSR-A) and peritoneal macrophages from MSR-A-knockout mice have shown that the MSR-A plays a major role in endocytic uptake of AGE-proteins by macrophages. Furthermore, in vitro experiments with rabbit arterial SMCs demonstrated a novel AGE-receptor mediating endocytosis of AGE-proteins. These in vivo and in vitro experiments suggest that AGE-proteins formed extracellularly in atherosclerotic lesions are endocytosed by macrophages through MSR-A in the early stage, and by SMCs through the novel AGE-receptor in the advanced stage, implicating functional contribution of the AGE-receptor-mediated interaction of AGE-proteins with these cells to atherosclerotic processes in arterial walls.

Animals↗

C-myc antisense oligodeoxynucleotides can induce apoptosis and down-regulate Fas expression in rheumatoid synoviocytes.

OBJECTIVE: To investigate the role of c-myc in the pathogenesis of rheumatoid arthritis (RA) and the mechanism of synovial apoptosis. METHODS: Using cultured human synoviocytes from patients with RA and c-myc antisense oligodeoxynucleotides (AS ODN), we examined the inhibition of cell proliferation by the MTT assay and the induction of apoptosis with TUNEL staining and fluorescence microscopy. In addition, the effect of c-myc on down-regulation of Fas expression was analyzed by flow cytometry, cytotoxicity assay, and reverse transcriptase-polymerase chain reaction. RESULTS: Treatment with c-myc AS ODN induced inhibition of cell proliferation, along with down-regulation of c-Myc protein and c-myc messenger RNA (mRNA) expression. The morphologic changes of synovial cell death were typical of apoptosis. In addition, c-myc AS ODN treatment down-regulated expression of Fas mRNA but not Fas antigen. Analysis of the involvement of the caspase cascade revealed that the cytotoxic activity of c-myc AS ODN was completely blocked by inhibitors of both caspase 1 (YVAD-FMK) and caspase 3 (DEVD-FMK). CONCLUSION: Our results strongly suggest that c-myc AS ODN might be a useful therapeutic tool in RA and clarify that cell death by c-myc AS ODN is induced through the caspase cascade, similar to Fas-induced apoptosis. In addition, combination therapy with anti-Fas antibody and c-myc AS ODN reduced Fas-dependent cytotoxicity.

Aged↗

Pulmonary alveolar proteinosis in infants.

UNLABELLED: We investigated the histological and molecular characteristics of pulmonary alveolar proteinosis (PAP) in two siblings (a brother and sister) who did not exhibit respiratory distress at birth but who each developed symptoms during infancy. Histological analysis of lung specimens showed positive staining for surfactant proteins in both patients. The polymerase chain reaction revealed expression of messenger RNA for surfactant protein B (SP-B) in the lung specimens. No defect in SP-B which is characteristic of the congenital form of PAP was observed. The concentration of surfactant protein A (SP-A) in bronchial alveolar lavage (BAL) fluid was elevated in patient 1 suggesting the BAL concentration of SP-A may be a clue to the diagnosis of this form of PAP. CONCLUSION: The accumulation of surfactant protein A in two siblings with an infantile form of pulmonary alveolar proteinosis could be a clue to the diagnosis.

Biopsy↗

Involvement of a MAP kinase, ZmMPK5, in senescence and recovery from low-temperature stress in maize.

Four species of protein kinase were identified in senescent maize leaves using a gel assay for kinase activity with myelin basic protein (MBP) as the substrate. Most of these kinases were also found in healthy green leaves that had been exposed to low-temperature stress (5 degrees C) and then returned to 25 degrees C. A 41-kDa protein was activated in senescent leaves, whereas a 45-kDa protein was activated 3 h after up-shift from 5 degrees C to 25 degrees C as well as in senescent leaves. A 39-kDa protein was activated by cold stress. The other two proteins, of 35 kDa and 52 kDa, constitutively phosphorylated MBP during senescence and temperature up-shift. Judging from their molecular masses, cation requirements and substrate specificities, it seemed likely that the 39-kDa, 41-kDa and 45-kDa proteins represented mitogen-activated protein kinases (MAPKs). Subsequently two MAPK cDNAs were isolated from a cDNA library constructed using mRNAs from senescent leaves. Northern analysis showed that the transcript corresponding to one of the cDNAs, designated ZmMPK5, accumulated in healthy leaves 3 h after the up-shift to 25 degrees C as well as in senescent leaves, suggesting that the 45-kDa protein kinase is encoded by ZmMPK5. Western analysis using an antiserum against the C-terminal region of ZmMPK5 showed that the level of the ZmMPK5 protein increased in senescent leaves. These results indicate that a 45-kDa MAPK is involved in the process of senescence and in recovery from low-temperature stress in maize plants.

Amino Acid Sequence↗

Application of three-dimensional CT angiography (3D-CTA) to cerebral aneurysms.

BACKGROUND: 3D CT angiography (3D-CTA) is a noninvasive imaging modality for cerebral aneurysms. 3D-CTA is helpful in the evaluation of the configuration of the aneurysm, the surrounding vessels, and the inside of the aneurysm dome. Clinical application of this technique in complicated large cerebral aneurysms showed that with 3D-CT endoscopic imaging, anatomical details of cerebral aneurysms such as the orifice of the aneurysm, intraluminal thrombus, and calcification of the wall could be clearly demonstrated. Using the 3D-imaging method with helical CT, virtual views of various surgical approaches can be compared preoperatively. This information was found to be very useful for determining difficult aneurysms for coil embolization or direct surgery including complicated and broad-based aneurysms. METHODS: Helical CT scanners (TOSHIBA X-vigor) are used for intracranial vascular lesions. At present, nearly stereoscopic images at a pixel size of 0.35 x 0.35 x 0.4 mm are obtained by reconstruction under the following conditions: slice thickness, 0.8 mm; couch top speed, 1.0 mm/ sec.; 130 kV; 220 mA; visual field, 18 cm in diameter (11 cm after extension); pitch, 0.4 mm; and opposed beam interpolation. RESULTS AND CLINICAL APPLICATION: By virtual vascular 3D-CT endoscopy, the lumen of the cerebral aneurysm is displayed by the surface rendering method. Its clinical applications include 1) Demonstration of three-dimensional aneurysm morphology, including the dome and the neck region; 2) Preoperative simulation; 3) Confirmation of parent blood vessels flowing into and out of aneurysms and visualization of aneurysmal lumen calcification. Coronal and sagittal sections can demonstrate whether the branches arise from the aneurysm or aneurysmal neck. The limitation of 3D-CTA is in delineating perforating arteries that are less than 1.2 mm in diameter. The problem with virtual vascular 3D-CT endoscopic images is that endoscopic findings in the vascular wall are incomplete because of the partial volume effect and pulsation of the aneurysm and vascular wall. CONCLUSIONS: Helical Scanning-CT (HES-CT) is an excellent noninvasive diagnostic modality for cerebral aneurysm detection. 3D-CT angiography has distinct advantages in evaluating aneurysms and selecting the most appropriate therapeutic modality.

Cerebral Angiography↗

Effect of intrinsic wetness and regional difference on dentin bond strength.

OBJECTIVES: The aim of this investigation was to determine the influence of intrinsic wetness on regional bond strengths of adhesive resins to dentin. METHODS: Human caries-free third molars were randomly divided into three groups for bonding: Group 1--no pulpal pressure; Group 2--pulpal pressure of 15 cm H2O; and Group 3--dentin dried overnight in a desiccator. Clearfil Liner Bond II (Kuraray) or One Step (Bisco) adhesive resins systems were applied to the flat dentin surfaces and the teeth were restored with APX resin composite (Kuraray). After 24 h in water at 37 degrees C, the specimens were sectioned into 0.7 mm thick slabs and divided into three regional subgroups according to the remaining dentin thickness and visual criteria: pulp horn, center, and periphery. The slabs were then trimmed for the micro-tensile bond test and subjected to a tensile force and crosshead of 1 mm/min. The data were analyzed with ANOVA and Fisher's PLSD test at a confidence level of 95%. The fracture modes were determined under a scanning electron microscope (JXA-840, JEOL, Japan). RESULTS: No significant regional difference was observed for the Group 1 and 2 specimens restored with Clearfil Liner Bond II (p > 0.05). However, bond strengths significantly decreased at the pulp horn region of the Group 1 and 2 specimens restored with One Step (p > 0.01). All bond strengths of Group 3 decreased significantly and regional differences were not evident (p > 0.05). SIGNIFICANCE: The dentin adhesive system should be chosen according to the substrate and region to be bonded, since bond strengths can vary according to the intrinsic wetness, region, and the adhesive system.

Dental Bonding↗

Tensile bond strength to and SEM evaluation of ground and intact enamel surfaces.

OBJECTIVES: The aim of this study was to evaluate the bonding of four commercially available adhesive systems to ground and intact enamel surfaces. METHODS: Extracted human teeth were used to measure the microtensile bond strength to enamel and a field-emission scanning electron microscopy (FE-SEM) was used to observe the bonded interface and the effect of the surface conditioning of each material. Intact buccal enamel surfaces were cleansed with tooth paste using a rotary dental brush, and the ground enamel surfaces were prepared by reducing approximately 0.5 mm from the buccal enamel surfaces using a high-speed diamond bur. One-Step (OS, Bisco), Single Bond (SB, 3M), Clearfil Liner Bond II (LBII, Kuraray), and Tokuso Mac Bond II (MBII, Tokuso) were evaluated for their ability to bond to enamel. RESULTS: There was no significant difference in bond strengths between the materials when they were applied to ground enamel surfaces (p > 0.05). However, the bond strengths of the self-etching systems, LBII and MBII, had significantly lower bond strengths to intact enamel than the bonding systems OS and SB using phosphoric acid etching (p < 0.05). FE-SEM revealed that the etching pattern of self-etching primers was not deep enough to obtain good penetration of bonding resin when applied to intact enamel surfaces. CONCLUSIONS: Phosphoric acid etching produced good resin adhesion to ground and intact enamel. The self-etching/self-priming systems also produced good adhesion to ground enamel, but had lower bond strengths to intact enamel.

Acid Etching, Dental↗

Tissue distribution of polaprezinc in rats determined by the double tracer method.

The tissue distribution of polaprezinc (an insoluble zinc complex of L-carnosine) in rats was studied by the double tracer method using [U-14C-histidine]-, 65Zn-polaprezinc. The 65Zn-radioactivity was measured with an auto-gamma counter, and the 14C containing 65Zn was converted to an absolute count according to the calibration curve for quenching with a liquid scintillation counter with the spill-over method. After the administration of 14C-, 65Zn-polaprezinc to rats, the excretion ratio and time courses in the tissues of the 14C-and 65Zn-radioactivity were different each other. We found that polaprezinc was metabolized as endogenous amino acid or zinc after dissociation in the body. The zinc concentration in plasma reached its maximum at 1 h and decreased slowly, returning to the endogenous level at 11 h after the administration of non-labeled polaprezinc. The concentrations of zinc in liver, kidney, testis, prostate, and cerebrum remained rather constant. The replacement ratios of 65Zn to zinc in the tissues at its maximum percentage were 40% in plasma, 16-20% in liver, kidney, blood, and prostate. The low replacement ratios in testis and cerebrum (2-3%) suggested that zinc uptakes in testis and brain were regulated by the blood-testis-barrier and blood-brain-barrier, respectively.

Administration, Oral↗

Objective scratch monitor evaluation of the effect of an antihistamine on nocturnal scratching in atopic dermatitis.

We previously reported a simple and easy-to-use device, Scratch Monitor for evaluation of nocturnal scratching. In the present study, the effect of an antihistamine (azelastine hydrochloride) on atopic dermatitis was investigated using this device. In 40 patients with atopic dermatitis, nocturnal scratching was measured by the monitor, when taking the drug and while off medication. Neither the 'sleeping time' nor the 'pre-asleep time' differed significantly, but there was a significant difference in 'scratch rate', 'minute scratch records', 'hourly awake number' and 'awake rate', which indicated that this drug alleviated nocturnal scratching and sleep disturbance. The difference was most prominent especially in patients with a serum IgE > or = 1000 IU/ml as well as in patients with mild symptoms and normal serum lactate dehydrogenase levels. The drug was more effective for nocturnal scratching in the early period, when the 'sleeping time' was divided into three equal parts (early, mid and late periods) and each period was compared.

Adolescent↗

Gibberellin-responsive genes: high level of transcript accumulation in leaf sheath meristematic tissue from Zea mays L.

In order to identify genes that are related to the gibberellin (GA) response in maize (Zea mays L.), mRNA species from wild-type and single-gene dwarf mutants, d5 and D8, were compared by fluorescent differential display. The d5 mutant is unable to produce biologically active GA, but recovers its tall stature on exogenous application of GA. D8 is insensitive to GA, despite the accumulation of a high level of endogenous GA, suggesting it to be a receptor mutant or a mutant in signal transduction pathway(s). After screening 7000 cDNA populations, one clone was isolated, for which transcripts were rare in d5 shoots but accumulated within 1 h after GA3 application. This clone, designated as ZmGR1a, encodes a polypeptide with a relative molecular mass of ca. 13 kDa, which shows significant homology to proline-rich proteins from several plant species. A similar experiment with D8 identified a clone, ZmGR2a, with low transcript levels, but accumulation within 6 h after GA3 treatment of d5 shoots. ZmGR2a encodes a polypeptide with a relative molecular mass of ca. 19 kDa, which shows no significant homology with any known protein. Southern blot analysis indicated that ZmGR1a and ZmGR2a form a small multigene family within the maize genome. In situ hybridization with wild-type seedlings showed transcripts on both to be abundant in leaf sheath meristematic tissue, in which GA enhances cell elongation and cell division.

Amino Acid Sequence↗

Patent ductus venosus.

BACKGROUND: Patent ductus venosus is extremely rare with only 14 cases reported in the world literature. We present a case of patent ductus venosus. METHODS AND RESULTS: A 29-year-old male was admitted with melaena stool caused by gastric haemorrhagic ulcers. Laboratory data disclosed severe anaemia; however, liver function tests were normal. Serum ammonia was also within the normal range. Serological viral markers for hepatitis B or C were all negative. The abdominal ultrasonography and computed tomography indicated a 12 mm diameter shunt located in the left lobe of the liver, which connected the portal vein with the left hepatic vein. After treatment for gastric ulcers, percutaneous transhepatic portography was performed and an enormous shunt connecting the umbilical portion of the portal vein with the left hepatic vein was revealed. CONCLUSIONS: Histological findings of the liver biopsy showed that portal venules could not be observed in the portal areas and that no fibrosis or inflammatory cell infiltration were shown. Because of the anatomical position of the shunt, the case was diagnosed as patent ductus venosus.

Adult↗

Re-entrainment of circadian rhythm of plasma melatonin on an 8-h eastward flight.

To estimate the process of re-entrainment we measured the melatonin rhythm on an eastward flight. After the baseline study, 24-hour blood sampling of six male subjects was done on the first and fifth days. During the daytime the subjects were exposed to natural zeitgeber outdoors every day except the blood sampling day. They were analyzed with an illuminometer when under the bright light condition. Four of the six subjects showed orthodromic re-entrainment, another subject showed antidromic re-entrainment, and the other subject kept the baseline pattern of plasma melatonin. The rate of re-entrainment in orthodromic re-entrainment was about 55 min per day. Measuring the circadian rhythm of plasma melatonin has clarified the interindividual re-entrainment difference.

Adaptation, Physiological↗

Metabolic fate of a new histamine H2-receptor antagonist, Z-300, in rat.

1. The metabolisms of (N-[3-[3-(piperidinomethyl)-phenoxy]-propyl]-2-(2-hydroxyethyl-1-t hio) acetamide.2-(4-hydroxy benzoyl) benzoate) (Z-300) in rat have been studied. 2. Five metabolites were identified, namely as sulphoxide (SO), sulphone (SO2), phenol (PH), propionic acid (PA) and thioglycolic acid (TH) derivatives. Furthermore, two metabolites, M1 and M2, were proposed as PH conjugated to sulphate and glucuronic acid respectively. 3. There were several metabolites in the plasma samples after oral administration of 14C-Z-300. The main metabolites were PH (mainly existing as the conjugates), PA and SO, and Z-300 was present as <10% of plasma radioactivity. SO2 and TH were barely detected in plasma. In the urine, the composition of metabolites was similar to that in the plasma. In the bile, the main metabolites were PH (mainly existing as the conjugates) and SO, and very little Z-300 was detected. In the faeces, the main compounds were Z-300 and TH, and very little SO. 4. During in vitro metabolism experiments, Z-300 was metabolized mainly in the liver, and a little in the kidney and lung. PH or its conjugates were produced little on the in vitro metabolism; this was different from that found in the in vivo experiment. The metabolism of Z-300 to SO appeared to be catalysed by cytochrome P450 rather than the flavin-containing monooxygenase. Both hepatic clearance calculated from the in vitro metabolism experiment (28.9 ml/min/kg) and from the liver perfusion metabolism experiment (33.2 ml/min/kg) were lower than the total clearance from the in vivo experiment (119 ml/min/kg). 5. After administration of 14C-SO into the caecum of rat, SO was converted to Z-300 and excreted in the faeces. 14C-SO was reduced by incubation for 4 h within the caecal content of rat under an anaerobic condition in vitro. The results suggest that SO was reduced to Z-300 by gut flora in the lower intestine.

Acetamides↗

Pharmacokinetics of a new histamine H2-receptor antagonist, Z-300, in rat and dog.

1. The plasma level of Z-300 reached a maximum (Cmax) at 30 min after the oral administration of Z-300 to dog, and disappeared from the systemic circulation with a half-life of 8-9 h. The bioavailability of Z-300 was 52% after the oral administration of Z-300, 3 mg/kg. At doses ranging from 3 to 30 mg/kg, Cmax and AUC (area under the plasma concentration-time curve) were proportional to the dose. 2. The plasma level of Z-300 reached Cmax at 10 min after the oral administration of Z-300 to rat, and disappeared from the systemic circulation with a half-life of 0.8-1.6 h. The bioavailability of Z-300 was 39% after the oral administration of Z-300, 10 mg/kg, and there was a non-linear relationship between the plasma level-time profile of Z-300 and the administered dose (3-50 mg/kg). 3. The binding of Z-300 to plasma protein was 92% in man, 65% in dog and 25% in rat. It is suggested that these species differences were due to the content of alpha1-acid glycoprotein (alpha1-AG), because Z-300 bound more strongly to alpha1-AG than to albumin.

Acetamides↗

Polyphasic taxonomy of the genus Shewanella and description of Shewanella oneidensis sp. nov.

The genus Shewanella has been studied since 1931 with regard to a variety of topics of relevance to both applied and environmental microbiology. Recent years have seen the introduction of a large number of new Shewanella-like isolates, necessitating a coordinated review of the genus. In this work, the phylogenetic relationships among known shewanellae were examined using a battery of morphological, physiological, molecular and chemotaxonomic characterizations. This polyphasic taxonomy takes into account all available phenotypic and genotypic data and integrates them into a consensus classification. Based on information generated from this study and obtained from the literature, a scheme for the identification of Shewanella species has been compiled. Key phenotypic characteristics were sulfur reduction and halophilicity. Fatty acid and quinone profiling were used to impart an additional layer of information. Molecular characterizations employing small-subunit 16S rDNA sequences were at the limits of resolution for the differentiation of species in some cases. As a result, DNA-DNA hybridization and sequence analyses of a more rapidly evolving molecule (gyrB gene) were performed. Species-specific PCR probes were designed for the gyrB gene and used for the rapid screening of closely related strains. With this polyphasic approach, in addition to the ten described Shewanella species, two new species, Shewanella oneidensis and 'Shewanella pealeana', were recognized; Shewanella oneidensis sp. nov. is described here for the first time.

Animals↗

Overexpression of a gene that encodes the first enzyme in the biosynthesis of asparagine-linked glycans makes plants resistant to tunicamycin and obviates the tunicamycin-induced unfolded protein response.

The cytotoxic drug tunicamycin kills cells because it is a specific inhibitor of UDP-N-acetylglucosamine:dolichol phosphate N-acetylglucosamine-1-P transferase (GPT), an enzyme that catalyzes the initial step of the biosynthesis of dolichol-linked oligosaccharides. In the presence of tunicamycin, asparagine-linked glycoproteins made in the endoplasmic reticulum are not glycosylated with N-linked glycans, and therefore may not fold correctly. Such proteins may be targeted for breakdown. Cells that are treated with tunicamycin normally experience an unfolded protein response and induce genes that encode endoplasmic reticulum chaperones such as the binding protein (BiP). We isolated a cDNA clone for Arabidopsis GPT and overexpressed it in Arabidopsis. The transgenic plants have a 10-fold higher level of GPT activity and are resistant to 1 microg/mL tunicamycin, a concentration that kills control plants. Transgenic plants grown in the presence of tunicamycin have N-glycosylated proteins and the drug does not induce BiP mRNA levels as it does in control plants. BiP mRNA levels are highly induced in both control and GPT-expressing plants by azetidine-2-carboxylate. These observations suggest that excess GPT activity obviates the normal unfolded protein response that cells experience when exposed to tunicamycin.

Amino Acid Sequence↗

Sucrose and Cytokinin Modulation of WPK4, a Gene Encoding a SNF1-Related Protein Kinase from Wheat.

WPK4, a gene encoding a putative protein kinase, was initially identified in wheat (Triticum aestivum) and shown to be up-regulated by light, nutrient deprivation, and cytokinins. To confirm that WPK4 has protein kinase activity, the protein was produced in Escherichia coli as a fusion protein with glutathione S-transferase. The purified protein exhibited autophosphorylation activity and phosphorylated both myelin basic protein and a peptide fragment of rice 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Levels of WPK4 transcripts in wheat seedlings were increased and decreased by the removal and addition of sucrose (Suc), respectively, to the culture medium. The introduction of the N-terminal kinase region of WPK4 into the yeast snf1 mutant cells, which cannot utilize Suc as a carbon source, rescued growth in Suc-containing medium. Cytokinins up-regulated the accumulation of WPK4 transcripts, but their effects were cancelled by the addition of Suc. Our results suggest that Suc negatively regulates the signaling pathway in which transcriptional activation of WPK4 is mediated by cytokinins.

Journal Article↗

Jasmonate-based wound signal transduction requires activation of WIPK, a tobacco mitogen-activated protein kinase.

A gene encoding a tobacco mitogen-activated protein kinase (WIPK) is transcriptionally activated in response to wounding. Transgenic tobacco plants, in which expression of endogenous wipk was suppressed, did not accumulate jasmonic acid or its methyl ester when wounded, suggesting that WIPK is involved in jasmonate-mediated wound signal transduction. Here, we demonstrate that activation of WIPK is required for triggering the jasmonate-mediated signal transduction cascade that occurs when wild-type tobacco plants are wounded. We also show that when plants are wounded, WIPK is rapidly and transiently activated, whereas the quantity of WIPK protein is maintained at a constant level. A transgenic tobacco plant in which the wipk gene was constitutively expressed at a high level showed constitutive enzymatic activation of WIPK and exhibited three- to fourfold higher levels of jasmonate than did its wild-type counterpart. This plant also showed constitutive accumulation of jasmonate-inducible proteinase inhibitor II transcripts. These results show that WIPK is activated in response to wounding, which subsequently causes an increase in jasmonate synthesis.

Cyclopentanes↗